Oxidative stress-induced S100B protein from placenta and amnion affects soluble Endoglin release from endothelial cells

Abstract

Oxidative stress with elevated intracellular Ca(2+) concentration as well as endothelial dysfunction is a component of pre-eclampsia. Our aim was to investigate the oxidative stress-dependent expression of Endoglin and Ca(2+)-binding S100B protein from villous and amniotic tissue cultures, and to assess sEng expression from S100B protein-stimulated endothelial cells. We initially examined Endoglin and Hydroxy-nonenal-(HNE)-modified proteins in the placentas and amnion obtained from women with pre-eclampsia (n = 8), and healthy controls (n = 8) by immunohistochemistry. To examine oxidative stress and the S100B protein effect on sEng expression from endothelial cells, normal villous and amniotic tissue cultures were stimulated by 4-HNE, sodium fluoride and xanthine/xanthine oxidase, whereas human umbilical vein endothelial cell cultures were treated with S100B protein in a dose- and time-dependent manner at 37 degrees C in an environment of 95% air and 5% of CO(2). Culture supernatants were assessed using ELISA. Cell viability was determined using MTS assay. The concentrations of sEng and S100B protein were significantly increased in the villous and amniotic tissue culture supernatants under oxidative stress. S100B protein-stimulated endothelial cells released sEng into conditioned media with a significantly higher expression levels at a concentration of 200 pM-20 nM S100B by 2 h, whereas treated with 200 nM of S100B endothelial cells significantly expressed sEng by 12 h and stimulated the cell proliferation by the same period of time. Our findings show that oxidative stress affects sEng and S100B protein expression from villous and amniotic tissues, and picomolar and low nanomolar concentrations of S100B protein significantly up-regulate sEng release from endothelial cells leading to endothelial dysfunction.

Gadd45α as an upstream signaling molecule of p38 MAPK triggers oxidative stress-induced sFlt-1 and sEng upregulation in preeclampsia

“…Gilbert et al (2009) have revealed that the hypertension produced by placental ischemia in pregnant rats is associated with increased sEng expression. Tskitishvili et al (2010) have also demonstrated that oxidative stress-induced S100B protein from the placenta and amnion affects sEng release from endothelial cells. However, the underlying mechanisms linking placental oxidative stress to the release of these two anti-angiogenic factors remain perplexing.…”

Inflammatory pattern recognition receptors and their ligands: factors contributing to the pathogenesis of preeclampsia

“…S100 Ca 2? -binding S100B protein is a RAGE ligand [73]. The concentrations of S100B protein were increased in the placenta under oxidative stress [73].…”

“…-binding S100B protein is a RAGE ligand [73]. The concentrations of S100B protein were increased in the placenta under oxidative stress [73]. S100B protein up-regulates sEng release from endothelial cells [73], and thus S100B protein is thought to be associated with preeclampsia.…”

Effects of 4-Hydroxy-2-Nonenal, a Major Lipid Peroxidation-Derived Aldehyde, and N-Acetylcysteine on the Cyclooxygenase-2 Expression in Human Uterine Myometrium

“…We have already reported that 4-HNE, a major end product of oxidative fatty acid metabolism, is accumulated in the placenta with CAM [12]. We also reported that oxidative stress affects sEndoglin and S100B protein expression from villous and amniotic tissues [13]. Oxidative stress has been postulated to be involved in the pathophysiology of numerous diseases [14,15].…”